New strategies for the production and screening of diverse organic molecules have recently emerged that can greatly facilitate the use of molecular structural information to discover novel ligands. The molecular structures studied in this Program Project-HIV gp41, HIV reverse transcriptase, cellular transcription factors for HIV replication--are current or potential targets for these approaches, and the specific aims of the various components involve their implementation. A chemistry core will provide support for chemical library synthesis and screening for various chemical syntheses. The core will be located within the new Harvard Institute for Chemistry and Cell Biology (ICCB), which will provide access to a large range of technologies and equipment and to new developments in combinatorial chemistry. The core will consist of one trained chemist (to be supervised by a senior chemist from the Institute), who will provide the following services: supply of monomers, linkers, encoding tags and beads, for library development within the individual projects; bead decoding; resynthesis of "hits" for re-testing; synthesis of focused libraries for determination of structure-activity relationships.